Mechanisms by Which Human Gliomas May Escape Cellular Immune Attack

Whereas substantial evidence indicates that the majority of glioma patients make humoral immune responses to their own tumours, the evidence that glioma patients make significant cellular immune responses is more tenuous and controversial. In order to study those properties of human gliomas that might contribute to their ability to escape cell-mediated immune attack, we have examined the ability of cultured human glioma cells to elicit allogeneic cytolytic lymphocyte responses in vitro. Five of ten glioma lines were unable to elicit allogeneic cytolytic lymphocyte responses in mixed lymphocyte-tumour cultures, despite the presence of serologically detectable alloantigens on the surface of the glioma cells. Analysis of the reasons why certain glioma lines failed to stimulate cytolytic lymphocyte responses revealed three distinct mechanisms by which human gliomas may escape cellular immune attack: 1. a defect in immunogenicity which can be overcome by "help" from an allogeneic mixed lymphocyte reaction, 2. the secretion of a protective mucopolysaccharide coat, and 3. the production of macromolecular immunosuppressive substance(s). The implications of these findings for the immunotherapy of human gliomas are discussed.